NF-κB is classically activated through dissociation from IκB in the cytoplasm [15]–[17], [20]–[22], [51]. DNA-binding and transactivation functions are also regulated through posttranslational modifications of NF-κB proteins in the cell nucleus. Phosphorylation at several sites by the IKK complex increases the DNA binding and transcriptional activities of p65 [20], [51], [55]. p50 phosphorylation by protein kinase A and other kinases is critical for binding of the p50 homodimer to DNA, which results in transcriptional repression of NF-κB dependent genes [18], [19]. In the apparent absence of changes in the p50 content, the downregulation of p50 homodimer DNA-binding in chronic alcoholics may occur due to the deficient phosphorylation of this protein (Figure 6).
